here is a SNAPSHOT of all what was presented at ESHRE this year. INFERTILITY UPDATED for all of you

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Helsinki, Finland, 3rd
to 6th
July 2016.

2. 1
Dear Colleagues,
Greetings from Emcure!
Recently, 32nd Annual Meeting of the European Society of Human Reproduction and
Embryology (ESHRE) was concluded at Helsinki, Finland from 3rd to 6th July 2016. Clinical
Gynaecologists, Infertility specialists and researchers, and of course, media descended on this
city to catch the latest updates on reproductive medicine. It is a pleasure to share with you
the recent scientific highlights of ESHRE-2016. We take priviledge to introduce to you our
unique endeavor EMSHOTS – Snapshots of ESHRE 2016. This booklet introduces you to top
clinical studies discussed at ESHRE 2016 in a simple, effective and seemigly readable manner.
We aimed to incorporate top 20 studies which may be a value addition to your practice. At
Emcure, Medical Team is tuned to upbring the latest scientific updates to your kind attention.
In this regard, we have made this update of ESHRE 2016. We have kept eye on different
aspects of reproductive medicine and infertility management while selecting studies from
ESHRE 2016. This booklet contains discussion of important keynote and invited sessions as
well as clinical studies such as ESPRAT trial, OPTIMIST Trial and some other clinical studies on
infertility management.
We hope this booklet will be a value addition and look forward to your feedback on this small
step to bring to you EMSHOTS – Snapshots of ESHRE 2016.
Please share your feedback at emquest@emcure.co.in OR call us on our toll free number
18002004048.
Regards,
Dr Rishi Jain
Director, Medical Services,
Emcure Pharmaceuticals Ltd. Pune

3. 2
Glimpses of ESHRE 2016, Helsinki, Finland (3 – 6 July, 2016)
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HHHuuummmaaannn RRReeeppprrroooddduuuccctttiiiooonnn aaannnddd EEEmmmbbbrrryyyooolllooogggyyy
Helsinki, Finland, 3rd
to 6th
July 2016.

4. 3
INDEX
Topics Page No.
ESHRE 2016 – Topline Studies 4
Keynote Session: Maternal Obesity - Long-term Consequences on Health of Offspring 5
Human Embryo Development: Microweel group culture dish Vs Standrd dish with individual droplets 6
Do Not Disturb Embryo till Day 5: RCT Preliminary Results 7
Very Young Woman: Aneuploidy Rates - A High Risk! 8
Occyte Donation Vs Autologus IVF: Perinatal Outcomes 9
Single Blastocyst Biopsy for Genetic Diseases and Aneuploidies: New Successful Approach 10
rLH Supplemetation for Controlled Ovarian Stimulation in Poor Ovarian Responders (Bologna
criteria): ESPART randomized controlled trial
11
OPTIMIST Trial: Individualized gonadotropin dosing in predicted poor responders undergoing IVF/ICSI 12
Invited Session - Embryo Selection: Non-invasive Markers 13
Invited Session - Donor Conception: Anonimity should not be Allowed! 14
Success of ART: How to Measure? Using National Registry Data 15
Ectopic Pregnancy Risk Factors in Assisted Conceptions: Human Fertilization and Embryology
Authority (HFEA) secondary analysis
16
Total FSH Dose Impact on Outcomes: Post-hoc analysis of the ESPART randomized controlled trial 17
Dehydroepiandrosterone administration does not increase pregnancy rates in poor responders:
Meta-analysis
18
Elevated Progesterone on Day of Triggering Final Oocyte Maturation: Significantly Predicts its
recurrence in Subsequent IVF Cycles
19
Oocyte Insemination of Injection: Effect of timing on Fertilization and Embryo Utilization 20
ICSI: For Non-Male Factor Infertility in Women 40 years and above 21
Early Pregnancy Loss in Frozen Embryo Transers: How should we limit it? 22
Age at Menarche and Menopause and Reproductive Lifespan: Risk of Cardiovascular Disease 23
Ovarian Response with Varying Gonadotropin Doses: Study in repeated stimulation cycles 24

5. 4
ESHRE 2016 – TOPLINE STUDIES/SESSIONS
--------------------------------------------------------------------------------------------------------------------------
Keynote Session: Maternal obesity and CV outcomes in offspring
“Maternal Obesity is associated with cardiovascular disease in later life of offspring. This
necessitates preventive measures to reduce obesity in women of reproductive age.”
--------------------------------------------------------------------------------------------------------------------------
ESPRAT Trial
“In patients with poor prognosis and even in poor ovarian reserve patients aligned to
Bologna criteria, addition of r-hLH to r-hFSH does not benefit in controlled ovarian
stimulation.”
--------------------------------------------------------------------------------------------------------------------------
Microwell Group Culture Vs Standard Dish with Individual Droplets: Embryo Development
“Use of microwell group culture benefits IVF outcomes and improves assessment and
follow up of each embryo quality. Quick morphology evaluation results in short time outside
incubator thus minimizing temperature and pH fluctuations.”
--------------------------------------------------------------------------------------------------------------------------
OPTIMIST Trial
“Individualized dosing of gonadotropins based on antral follicle count predicted poor
responsers is not associated with improved live birth rates. Higher oocyte retrieval and few
cycle cancellation with adjusted treatment do not lead to improved advantageous outcomes
compared to standard dosing.”
--------------------------------------------------------------------------------------------------------------------------
Non-Invasive Markers for Embryo Selection
“Morphological assessment in hands of experienced embryologist: best available
method for embryo selection till others methods are proved.”
--------------------------------------------------------------------------------------------------------------------------

6. 5
Keynote Session: Maternal Obesity
Long-term Consequences on Health of Offspring
Ref: Eriksson J. O-002 Long-term consequences of maternal obesity on the health of offspring Abstracts of the 32nd Annual
Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016.
Abstract
 Developmental Origins of Health and Disease (DOHaD) hypothesis
o Non-communicable diseases (e.g CAD, T2DM): origins in prenatal and early
childhood life
 Intrauterine environment affected by many factors
 Maternal Characteristics: can have impact on fetal development that determines
future health outcomes
 Association of maternal obesity and offspring health outcomes: Recent investigation
have confirmed
 Prevalence: women in reproductive age - 1/3rd
overweight and 1/5th
obese
 Maternal obesity: adverse maternal & neonatal outcomes
 Higher risk of conenital defects and miscarriages
 Higher risk of premature death in adult offspring
 Helsinki Birth Cohort Study: Increasing maternal BMI – Higher risk of cancer,
CV disease, T2DM in offspring
 T2DM association is stronger in women
 Maternal BMI association with offspring BMI
 Less favorable body composition
 Affects body fat percentage in offspring’s adult life
o Low maternal BMI-High offspring birth weight: Lower fat percentage
o High Maternal BMI- High offspring birth weight: Higher fat percentage
“CLINICAL PEARL”
Maternal adiposity and prenatal environment leads to detrimental body composition
programming in early life and is a interplay of environmental, genetic and epigenetic
mechanisms. This explains in part the association of maternal obesity and later CV disease in
offsprings. Preventive measures need attention to reduce obesity in women of reproductive age.

7. 6
Ref: Fancsovits P, et al. O-007 Prospective randomized study comparing human embryo development in a microwell group
culture dish (Primo Vision dish) or in a standard dish with individual droplets Abstracts of the 32nd Annual Meeting of
ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016.
STUDY DETAILS
 Design: Prospective, Randomized Study
 Population: Patient subjected for IVF-ET
 Simulataneous culture of more than one embryo in same microdrop may result in
accumulation auro- as well as para-crine factors
 Study Groups: Five hundred thirty two IVF-ET cycles; Culture in microwell group
culture dish (PrimoVision, Vitrolife) (n=264 cycles) Vs individual microdrop culture
in conventional Petridish (n=268 cycles)
 Microwell group culture: 9 microwells, well to well distance, facilitates paracrine
effects, specific well morphology facilitates autocrine effects
 Oocyte fertilization performed by conventional IVF or ICSI
 Outcome assessed: Fertilization rate, embryo development, clinical pregnancy rate and
embryo utilization rate
Human Embryo Development:
Microwell group culture dish Vs Standard dish with individual droplets
“CLINICAL PEARL”
Use of microwell group culture benefits IVF outcomes and improves assessment and follow up of
each embryo quality. Quick morphology evaluation results in short time outside incubator thus
minimizing temperature and pH fluctuations.
RESULTS
 Characteristics: female age, length of stimulation, gonadotrophin dose, number of oocytes and
number of transferred embryos: Were similar among two groups
 Fertilization rate in IVF cycles: Similar in two groups
Fertilization rate in ICSI cycle No. of blastomeres on Day 3 Clinical pregnancy rate
 Multiple pregnancy rate: Significantly higher in Study Group (28.5% vs. 40.5%; P = 0.044)
 Implantation rate: Similar in two groups (30.1% vs. 27.0%; P = 0.265).
 Embryo for cryopreservation (day 3): Significantly higher Study Group (39.7% vs. 32.1%; P = 0.024)
 Embryo utilization rate: Significantly higher in microwell group (81.3% vs. 74.7%; P < 0.001)
 Time needed for Morphology evaluation: Significantly less with study group (144 ± 70 vs. 175 ± 73
s/cycle; P < 0.001)
70.60
%
64.90
%
Study Group Control Group
FertlizationrateICSI(%)
P=0.001
7
6.7
Study Group Control Group
Numberofblastocysts
P=0.013
50.80
%
40.60
%
Study Group Control Group
Clinicalpreganncyrate(%)

8. 7
Ref: Ten et al. O-008 Do not disturb the embryos until day 5: preliminary results of a double blind prospective randomized
controlled trial Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human
Reproduction vol.31 Supp.1, 2016.
STUDY DETAILS
 Design: Randomized, double-blind, controlled trial
 Population: Patients receiving first IVF therapy with anonimity in oocyte donation
 N=130 IVF cycles
 Study Groups: Study group (non-embryonic observation, 586 cycles) Vs control group
(conventional observation on day 2 and 3, 305 cycles)
 Results of 130 IVF treatments: study group (n=67) and control group (n=63).
 Duration: 3 years
 Assessment Parameters: Blastocyst formation rate and clinical outcomes
Do Not Disturb of Embryo till Day 5:
RCT Preliminary Results
RESULTS
Parameter Control Group Study Group P value
Donated eggs 11.3 ± 2.1 11.1 ± 2.0 -
Fertilization rate 78.4% 75.0% P=0.2
Embryo to reach blastocyst stage (d-5) 60.6% 62.1% P=0.7
Embryos transferred 1.5 ± 0.5 1.4 ± 0.5 P=0.1
Implantation Rates* 47.4% 44.0% P=0.7
Ongoing pregnancy rate 47.5% 43.1% P=0.7
*In embryos with evaluation performed on day 2, 3 and 5 compared (control) to embryo which were
cultured till blastocyst stage and then eveluated (study)
These results are preliminary results of a larger RCT. So final results will be awaited to prove the
hypothesis.
“CLINICAL PEARL”
Single assessment of embryo on day 5 is not associated with any adverse outcomes when
compared to embryo evaluation on day 2 and 3. Such day 5 assessment of embryos prior to
rtansfer or freezing provides similar results. Thereby reduces cost burden on couples. This
makes it questionable whether conventional day 2 and 3 assessments of embryos provide any
predictive value or not.

9. 8
Ref: Eva M. G, et al. O-011 Very young women are at risk of having a high embryo aneuploidy rate. Abstracts of the 32nd
Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016.
STUDY DETAILS
 Age < 22: Women have high risk of embryo aneuploidy
 Study Design: Retrospective, observational
 N=1040 blastocysts (376 comprehensive chromosome screening (CCS) cycles)
 Preimplantation genetic screening (PGS): Previous clinical history of repetitive
miscarriage, recurrent implantation failure or severe male factor; Women: 19 to 45 y
 Objective: To assess prevalence of embryo aneuploidy rate in very young women
Very Young Woman: Aneuploidy Rates
A High Risk!
RESULTS
 CCS assessed in 97.2% of the biopsied embryos
 Overall embryo aneuploidy rate: 40.6%
 Embryo aneuploidy rate: Increased with age following a fifth order exponential curve
(significant distribution with p<0.05)
 HIGHEST embryo aneuploidy rate: at 43 years (83.3%)
 In < 30 years: HIGHEST embryo aneuploidy rate: at 21 years (52.2%)
 LOWEST embryo aneuploidy rate: at 22 and 25 years (24.1%)
 Embryo aneuploidy rate in < 22 years: 40.0%
 To reduce confounding, aneuploidies of 99 polar bodies in young women (19 to 31 years)
were performed
o In 93% of the biopsied oocytes: polar body aneuploidy rate - 18.5%
o No difference in the results of polar body aneuploidies and age
“CLINICAL PEARL”
Study finds that aneuploidy rates in women < 22 years is high but similar to the women aged 34
years. Evaluation with higher sample size is needed to confirm or refute the findings and also to
assess the effect of polar body.

10. 9
Ref: Kamath et al. O-014 Perinatal outcomes following oocyte donation versus autologous IVF: analysis of 99,111 singleton
live births. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction
vol.31 Supp.1, 2016.
STUDY DETAILS
 Anonymous data: Human Fertilization and Embryology Authority (HFEA), the
statutory regulator of assisted reproduction treatment (ART) in the UK.
 Population: women who underwent ART from fresh oocyte donation or autologous
IVF cycles
 Study Groups: Fresh oocyte donor (n=524,489) and autologous IVF cycles (n=99,111)
resulting in singleton live births
 Objective: To study perinatal outcomes of preterm birth (PTB) and low birth weight
(LBW)
 Logistic regression: performed adjusting for female age category, year of treatment,
number of previous IVF cycles, type of infertility, causes of infertility, number of
oocytes retrieved and initial multiple vs. singleton gestation leading to singleton live
birth
Occyte Donation Vs Autologus IVF:
Perinatal Outcomes
“CLINICAL PEARL”
Occyte donation is associated with increased risk of PTB and LBW. This needs to counselled to
the patients and couples who are engaged in donor oocyte rleated IVF.
RESULTS
 Unadjusted odds of PTB: Significantly higher in oocyte donation compared to autologus IVF
Outcome Category Unadjusted Odds Ratio
(95% CI)
Adjusted Odds Ratio
(95% CI)
Preterm birth (PTB) 2.24 (1.71 – 2.93)* 2.29 (1.73 – 3.03)*
Early PTB 1.97 (1.13 – 3.44)* 1.63 (0.91 – 2.91)
Low Birth Weight (LBW) 1.98 (1.50 – 2.63)* 2.00 (1.50 – 2.69)*
Very LBW 1.60 (1.15 – 3.0)* 1.29 (0.67 – 2.49)
*significant finding

11. 10
Ref: Cursio E, et al. O-027 Genetic diseases and aneuploidies can be detected with a single blastocyst biopsy: a new clinical successful
approach. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1,
2016.
STUDY DETAILS
 Design: Consecutive case series study
 Total 963 blastocysts obtained in 264 PGD (preimplantation Genetic Diagnosis) cycles
 Preimplantation Genetic Screening (PGS) used for ploidy status from same biopsy when
blastocyst resulted transferable after the PGD
 To study utility of single blastocyst biopsy to detect efficiently both genetic diseases and
aneuploidies and assess Clinical and biological outcomes
Single Blastocyst Biopsy for Genetic Diseases and Aneuploidies:
New Successful Approach
“CLINICAL PEARL”
Dual genetic testing lead to higher cycle cancellation rate necessitating proper informed consent
before procedure. Biopsy performed to prevent hereditary disease transmission, genetic status
of blastocyst should also be mandatorily analysed to avoid use of useless embryo transfer.
Blastocyst is more convenient stage to perform biopsy.
RESULTS
 Mean Age of Women: 35.26 ± 4.16 years
 Mature oocytes injected: 2389
o Fertilization rate: 75.1% (1795/2389)
 Embryos obtained: 1780
 Blastocyst formation: 54.1% (963/1780)
o Biopsied (Day 4-7): 952
 Blastocyst transferable after genetic analysis: 269
 Embryo transfer performed: 174 (53 fresh and 121 cryopreserved)
o Total healthy or carrier euploid blastocysts transferred: 184
 Outcomes from 174 embryo trnasferred
 Clinical Pregnancies: 82 (47.1%)
 Heart Beat: 85 (implantation rate of 46.2%)
o Miscarriages: 17 (9.8%)
o Ectopic Pregnancy: 1 (0.6%)
 Deliveries completed: 53
o Pregnancies ongoing: 11
 Babies born: 56, healthy, 28 males and 28 females
 Transferable blastocyst cryopreserved: 111 (from 49 cycles)

12. 11
Ref: Humaidan et al. O-033 Results of the ESPART randomized controlled trial investigating recombinant luteinizing hormone
supplementation for controlled ovarian stimulation in poor ovarian responders aligned with the Bologna criteria. Abstracts of the 32nd
Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016
rLH Supplemetation for Controlled Ovarian Stimulation in Poor Ovarian Responders
(Bologna criteria): ESPART randomized controlled trial
STUDY DETAILS
ESHRE Bologna Criteria: For identifying standardized population to include in clinical trials
investigating poor ovarian response (POR)
 Design: Phase 3, Randomized, single-blind, parallel-group, active-comparator trial
 Population: controlled ovarian stimulation (COS) performed in women with poor
ovarian response (POR) (previous cycle with ≤3 oocytes retrieved with conventional
stimulation; anti-Müllerian hormone (AMH) level 0.12–1.3 ng/mL.)
 N=939
 Study Groups: fixed-ratio r-hFSH plus r-hLH (2:1 ratio) (n=462) or r-hFSH
monotherapy (n=477)
 Primary endpoint: number of oocytes retrieved
 Secondary and other outcomes: biochemical, clinical and ongoing pregnancy rates,
embryo implantation rate and live birth rate.
RESULTS
 Mean age: 38.3 years, Mean AMH level: 0.59 ng/mL, Mena antral follicle count: 4.8
 One previous ART with 3 or less occyte retrieved: 83%
Outcome Characteristic r-hFSH plus r-hLH r-hFSH
Number of oocytes retrieved (mean/SD) 3.3 (2.71) 3.6 (2.82)
Biochemical pregnancy rate* 17.3% 23.9%
Clinical pregnancy rate 14.1% 16.8%
Ongoing pregnancy rate 11.0% 12.4%
Live birth rate 10.6% 11.7%
Incidence of adverse events 25.8% 33.3%
*significant difference
 No subpopulation was identified that benefitted from the addition of r-hLH to r-hFSH.
“CLINICAL PEARL”
In patients with poor prognosis even in POR patients aligned to Bologna criteria, addition of
r-hLH to r-hFSH does not benefit in controlled ovarian stimulation.

13. 12
Ref: van Tilborg et al. O-035 Optimization of outcome through individualized dosing in predicted poor responders undergoing IVF/ICSI;
the OPTIMIST randomized controlled trial, NTR2657. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July
– 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016
OPTIMIST Trial:
Individualized gonadotropin dosing in predicted poor responders undergoing IVF/ICSI
STUDY DETAILS
 Design: Multicenter cohort study
 Population: Women with predicted poor response starting their first IVF/ICSI cycle
 Poor response: Antral follicle count (AFC) < 11 follicles sized 2–10 mm
 N=501
 Study Groups: Adjusted [n=238] (225 (AFC 8–10) [n=131] or 450 IU FSH (AFC < 8)
[n=107]) and standard dose of 150 IU FSH [n=263]
 Primary Outcome: Ongoing pregnancy leading to live birth <18 months after
randomization
RESULTS
Rate of cumulative ongoing
pregnancies leading to live birth rate
Parameters Adjusted
TT
Standard
TT
RR / Mean Diff.
(95% CI)
Avg time to positive
pregnancy (months)
5.1 4.5 -
Live birth rate
(First cycles)
18% 18% 1.0 (0.7 – 1.5)
Oocytes Retrieved 7.6 6.5 1.1 (0.2 – 2.0)
Cycle Cancellation Rate
(First cycles)
8% 23% 0.3 (0.2 – 0.6)
Reason for cancellation –
Poor resposne
7% 21% 0.32 (0.19 – 0.54)
TT: Treatment
“CLINICAL PEARL”
Individualized dosing of gonadotropins based on antral follicle count predicted poor responsers is
not associated with improved live birth rates. Higher oocyte retrieval and few cycle cancellation
with adjusted treatment do not lead to improved advantageous outcomes compared to standard
dosing.
41% 41%
Adjusted TT Standard TT
Risk Ratio: 1.0 [CI 95% 0.8–1.2]

14. 13
Ref: Sallam HN. O-045 Non-invasive markers for embryo selection. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki,
Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016
INVITED SESSION
Embryo Selection: Non-invasive Markers
Abstract
 Need – of a reliable noninvasive method or marker to select embryo for IVF
o This can improve live birth rates and reduce multiple pregnancies and complications
o Evaluation of such methods requires constuction of receiver operating characteristic
(ROC) curve followed by a randomized trial (RCT) in single embryo transfer cycles
 Older Approaches
 Embryos were selected based on morphology at
o Pro-nuclear stage / Cleavage stage / Blastocyst stage
o Blastocyst stage: Small but significantly higher live birth rate compared to cleavage stage
transfer
 More subjectivity to morphological selection was attempted
o Graduated embryo score / computerized transformation of the embryo picture into a
mathematical vector: BUT NO SUPERIORITY was seen
 Recent Approach
 On Basis of morpho-kinetics studied by time lapse photography (TLP): Algorithms are
constructed based on defined kinetic and morphologic markers
o However, Cochrane review and recent RCT – suggest insufficient evidence of differences
in live birth or clinical pregnancy between TLP and conventional incubation
 Selection on the basis of oxygen consumption (OC): RCT needed
 Biochemical markers
o Pyruvate and glucose uptake as well as lactate production
o Glucose uptake on day 4: Significantly high in embryos resulting in pregnancy
o Amino acids turn-over rate: Different patterns in embryos resulting in pregnancy
o Embryo metabolomics by spectroscopic analysis or by nuclear magnetic resonance has
been tried
o Soluble human leukocytic antigen G (s-HLA-G) fragment: good predictor of embryo
viability: RCT needed
o Others: β-HCG, haptoglobin-α-1 fragment and platelet activating factor (PAF)
o Oxidative Stress measurement: Promising but RCT needed
“CLINICAL PEARL”
MORPHOLICAL ASSESSMENT in hands of experienced embryologist: BEST AVAILABLE
METHOD for embryo selection till others methods are proved.

15. 14
Ref: Thorn P. O-050 Anonymity in donor conception should not be allowed. Abstracts of the 32nd Annual Meeting of ESHRE,
Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016
INVITED SESSION
Donor Conception: Anonimity should not be Allowed!
Abstract
 Anonimity is frequent in donor conceptions
 Anonimity refers to the semen or egg donor/s being nameless for intended parent and
child.
 A common practice till 90s, anonimity was witnessed with some fears – child may
confused about “real” parents, social bonding between child and parents may be less
secure if child was aware of of his/her conception, donors had no protection from legal
paternity.
 Over past two decades, it has changed substantially.
 Legislative actions are in force in many countries
o Offsprings has right to access donor’s identity
o Donors are exempted from parental rights or responsibilities
 Though practice is changing, a debate of anonimity and identifiable donors remains
controversial.
 Legisltaion has important role in this process: Donor’s identity remains shielded.If
anonimity is abolished-Number of donors may go down significantly; Family harmony
may get strained if child becomes aware of donor
 In other countries – Legisltaion has contradictory messages and ambiguities are raised as
it lets offspring the right to access the biological origin and do not protect donors
sufficiently from responsibilities
 This suggests in continuation of past anxieties, the stigma surrounding such new family
compositions continues
o Discontinuing Anonimity has advantages: Avoids frustration of offsprings /
Provide equal rights as adoptees
 Anonimity is hazardous
o Both parents and children – Project unrealistic fantacies about the donor and may
makes them unable to adjust to reality
o Limits information that donors receive about outcome of donation and very little
is known about their needs
“CLINICAL PEARL”
A Multilevel Approach to tackle Anonimity is the need
 Individual level: Pre-treatment/pre-donation counselling to donors and parents
 Professional level: Framework for counselling imbedded in medical treatment
 Macro-level legislative frameworks: Protect the donor from responsibilities, that grant
parents unambiguous legal maternity/paternity and offspring the right to access their
biological origins

16. 15
Ref: Chambers et al. How to measure success in ART: Using national registry data to inform patient, provider and policy decision making.
Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31
Supp.1, 2016
Success of ART: How to Measure?
Using National Registry Data
STUDY DETAILS
 Design: population based study (Information on ART cycles was sourced from the
Australian and New Zealand Assisted Reproduction Database (ANZARD))
 Population: Women taking ART Treatments
 N= 39,698 women
 Study Method: Women who had their first fresh ART cycle between 2009 and 2011 were
followed through all fresh and thaw cycles to 2013 to calculate cumulative live birth rates
 Different dimensions (efficacy, effectiveness, safety, and equity) and perspectives
(patient, health provider, funder, society) of measuring success in medicine were used
 Objective: To assess most appropriate and relevant measures of ART success
RESULTS
 Cycle-based success rates: Vary on selection of numerator and denominator
o 13.2% for Birth Emphasizing a Successful Singleton at Term (BESST)
o 31% for clinical pregnancy per embryo transfer
 Cumulative live birth rates per woman:
o vary based on the definition of a cycle [a single cycle or a complete cycle] patient
age, and assumptions about women who stop treatment without achieving a
pregnancy
o ~30% points between conservative and optimistic assumptions – about women
who discontinue treatment and based on cycle definition
“CLINICAL PEARL”
While measuring ART success, the choice of such measurement should reflect intention of
treatment and the target audience. ART registry data can provide information on likelihhod of
success over successive treatment cycles and time, inform about clinic success and help guide
policies.

17. 16
Ref: Bhattacharya S, et al. O-067 Risk factors for ectopic pregnancy in assisted conceptions: secondary analysis of human fertilization and
mbryology authority (HFEA) data. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016.
Human Reproduction vol.31 Supp.1, 2016.
Ectopic Pregnancy Risk Factors in Assisted Conceptions:
Human Fertilization and Embryology Authority (HFEA) secondary analysis
STUDY DETAILS
 Design: Case Control study
 Population: HFEA data for first cycles only
 N= 99,528 pregnancies analysed/1,285 ectopic
 Study Method: Risk factors assessed were age of women, year of procedure, primary or
secondary infertility, duration of infertility, causes of infertility, type of ART procedure,
fresh or frozen cycle and number of embryos transferred.
 Objective: To study risk factors for ectopic pregnancy (EP) in a population receiving
fertility treatment
RESULTS
 Incidence of ectopic pregnancy: 1.31% (95% Confidence Intervals 1.30, 1.32)
 Risk Factors Identified for EP
 Tubal disease: Strongly associated with the risk of EP
 Univariate [1.63 (95% CI 1.37, 1.93)]
 Multivariate [1.89 (95% CI1.59, 2.25)]
 Low sperm motility [adjusted OR 1.90 (1.23–2.94)],
 With increasing number of embryos transferred, risk of EP increased linearly
 2 - adjusted OR 1.18 (95% CI 1.02–1.38)
 3 - adjusted OR 1.35 (1.21–1.50)
 4 or more - adjusted OR 1.02 (0.85–1.22)
 Increasing age: Reduced risk on univariate analysis but not on multivariate analysis
 No increase in EP risk with increasing year of procedure or duration of infertility. Secondary
versus primary infertility was also not found to be a significant factor.
“CLINICAL PEARL”
Association of ectopic pregnancy with ART procedures reduce chances of successful treatment.
Single embryo transfers may reduce the risk of ART associated EP.

18. 17
Ref: Hubbard S, et al. O-081 The impact of total follicle-stimulating hormone (FSH) dose on outcomes in ESHRE Bologna poor ovarian
responders. A post-hoc analysis of the ESPART randomized controlled trial. Abstracts of the 32nd Annual Meeting of ESHRE,
Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016.
Total FSH Dose Impact on Outcomes:
Post-hoc analysis of the ESPART randomized controlled trial
STUDY DETAILS
 Design: post-hoc analysis of the ESPART study, a RCT.
 Population: poor ovarian responders (PORs) undergoing controlled ovarian stimulation
with recombinant-human FSH (r-hFSH) or r-hFSH plus recombinant-human luteinizing
hormone (r-hLH)
 N=r-hFSH+r-hLH, n = 427; r-hFSH, n = 445
 Study Method: Number of oocytes retrieved, ongoing pregnancy rate (OPR), and live
birth rate (LBR) over a single ART cycle were determined
 Dose groups: <3000 IU, 3000 to <4000 IU, 4000 to <5000 IU and ≥5000 IU
 Objective: To study FSH dose influence outcomes for poor ovarian responders (PORs)
RESULTS
 Total mean FSH dose: Similar in both arms
FSH Dose <3000 IU 3000 to <4000 IU 4000 to <5000 IU ≥5000 IU
Mean Age (SD) 37.9 (3.2) 38.3 (3.0) 38.5 (2.8) 38.2 (2.9)
Number of oocytes retrieved,
mean (SD)
r-hFSH 3.3 (2.38) 4.4 (3.15) 3.7 (2.31) 2.9 (2.30)
r-hFSH+r-hLH 3.3 (2.29) 4.2 (2.97) 3.5 (2.32) 2.7 (2.15)
Ongoing pregnancy, n/N (%)
r-hFSH 2/34 (5.9) 29/183 (15.8) 17/141 (12.1) 10/87 (11.5)
r-hFSH+r-hLH 7/61 (11.5) 27/179 (15.1) 15/111 (13.5) 3/76 (3.9)
Live birth, n/N (%)
r-hFSH 2/34 (5.9) 28/183 (15.3) 16/141 (11.3) 9/87 (10.3)
r-hFSH+r-hLH 7/61 (11.5) 26/179 (14.5) 14/111 (12.6) 3/76 (3.9)
“CLINICAL PEARL”
PORs: Max responses with 3000 to <5000 IU FSH. Outcomes for PORs not responding to these
doses are unlikely to improve at higher doses, while lower doses seem insufficient. Different
pregnancy and live-birth outcomes observed at <3000 and ≥5000 IU with/without LH
supplementation warrants further investigation.

19. 18
Ref: Kolibianakis E, et al. O-084 Dehydroepiandrosterone administration does not increase pregnancy rates in poor responders: a meta-
analysis. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction
vol.31 Supp.1, 2016.
Dehydroepiandrosterone administration does not increase pregnancy rates in poor
responders: Meta-analysis
STUDY DETAILS
 Population: RCTs evaluating DHEA administration exclusively in poor responders
undergoing IVF
 Intervention: DHEA Vs No DHEA administration in poor responders
 Method: literature search - MEDLINE, CENTRAL and Web of Science until January
2016, RCTs evaluating DHEA administration exclusively in poor responders undergoing
IVF.
 Objective: To determine whether dehydroepiandrosterone (DHEA) administration
improve the probability of pregnancy in poor responders undergoing ovarian stimulation
for IVF
 Main outcome: Achievement of pregnancy (clinical pregnancy or as live birth)
 Secondary outcome: duration of stimulation, total units of gonadotrophins required,
number of cumulus-oocyte complexes (COCs) retrieved, number of 2-pronuclei oocytes
and number of embryos transferred.
RESULTS
 Compared to no DHEA treatment, DHEA administration for 6 – 12 weeks: No increase in
probability of
o Clinical pregnancy (RR: 1.10; 95% CI: 0.81–1.50) or
o Live birth (RR: 1.18; 95% CI: 0.36–3.88)
 DHEA associated with
 Significant decrease
o Total units of gonadotropin required (WMD: −783.9 IU, 95% CI: −1065.6 to −502.3)
 No significant differences
o Duration of stimulation (WMD: −1.25 days, 95% CI: −2.53 to +0.03)
o Number of COCs retrieved (WMD: +0.66 COCs, 95% CI: −1.88 to +3.19)
o Number of 2-pronuclei oocytes (WMD: +1.13 2pn, 95% CI: −0.32 to +2.58)
o Number of embryos transferred (WMD: +0.53 embryos, 95% CI: −0.24 to +1.30)
“CLINICAL PEARL”
Poor ovarian response definition varied in most studies. This metanalysis restricted to the studies
exclusively in poor responders suggested that DHEA administration does not improve pregnancy
rates in such patients. This necessitates counselling of poor responders for unrealistic expectations
regarding their prognosis.

20. 19
Ref: Venetis et al. O-085 Elevated progesterone on the day of triggering final oocyte maturation significantly predicts its reoccurrence in a
subsequent IVF cycle. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human
Reproduction vol.31 Supp.1, 2016.
Elevated Progesterone on Day of Triggering Final Oocyte Maturation: Significantly
Predicts its Recurrence in Subsequent IVF Cycles
STUDY DETAILS
Progesterone elevation (PE) on the day of triggering final oocyte maturation is associated with
the magnitude of the ovarian response to stimulation and is a significant predictor of its
reoccurrence in a subsequent IVF cycle.
 Design: Retrospective analysis
 Population: fresh IVF/ICSI cycles
 N = 1,702 cycles (197 patients contributed to 2 or more cycles)
 Objective: To study whether PE on the day of triggering final oocyte maturation during
an IVF cycle increase the risk of PE in subsequent cycles.
RESULTS
 No of Cycles: Two: 168, Three: 25, Four: 4
 In 230 cycles -
o 15 had PE [previous cycle included in study sample] (6.5%, 95% CI: 4.0–10.5)
o 22 had PE [Histroy of PE in a prior cycle] (9.6%, 95% CI: 6.4–14.1)
 6 (out of 22) had reoccurence of PE
o 9 (out of 208) who had PE had no prior history of PE
 Generalized Estimating Equation (GEE): for the prediction of PE occurrence and also to adjust
for the intensity of ovarian stimulation.
 PE on the day of hCG in a previous cycle:
o Significant association with an increased risk of PE in a subsequent cycle OR: 8.4, 95%
CI: 2.8–24.9
 Adjusted risk of PE
o For cycles without history of PE 4.3% (95% CI: 1.5–7.0)
o For cycles with history of PE 27.3% (95% CI 10.3–44.3)
 In full model adjusting for the intensity of ovarian stimulation: history of PE was still a
significant predictor (OR: 6.26, 95% CI: 1.81–21.62).
“CLINICAL PEARL”
Identifying patients with prior history of PE are likely have reoccurrence in subsequent cycles.
Clinicians should opt for approach to reduce PE by using milder stimulation protocols.
Counselling on increased probability of freezing all embryos or deferring embryo trasnfer need to
be done.

21. 20
Ref: Desmet B, et al. O-092 Effect of the timing of oocyte insemination or injection on the fertilization and embryo utilization rates in
assisted reproduction. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human
Reproduction vol.31 Supp.1, 2016.
Oocyte Insemination of Injection:
Effect of timing on Fertilization and Embryo Utilization
STUDY DETAILS
 Design: Single-centre, Retrospective, Cohort analysis
 Population: Women undergoing IVF or ICSI cycles using fresh autologous gametes
 N= 1696 IVF and 14,553 ICSI cycles
 Methods: Time between ovulation triggering and oocyte insemination/injection grouped
as 7 regular 1 h-interval categories: <36, 36, 37, 38, 39, 40 and ≥41 h.
 Outcome Measure: Fertilization and utilization rates (embryos adequate for transfer or
cryopreservation) per inseminated cumulus-oocyte complex for IVF or per MII for ICSI
RESULTS
 Total: 16,866 inseminated (IVF) and 104,593 injected (ICSI) oocytes analuysed
 For IVF Group
 No significant differences in the
o Adjusted Fertilization rate: Range: 57.4–62.9%
o Adjusted Utilization rate: Range: 30.4–34.8%
 For ICSI Group
 Adjusted Fertilization Rates for the interval
o <36 h: 71.0 (slightly but significantly lower compared to other groups)
o 36: 78.3 / 37: 77.6 / 38: 78.0 / 39: 78.9 / 40: 79.3 / ≥41: 79.9%
 Adjusted Utilization Rates: No difference in all time intervals
o < 36: 41.4 / 36: 44.3 / 37: 43.1 / 38: 45.5 / 39: 44.8 / 40: 43.9 / ≥41: 43.8%
“CLINICAL PEARL”
This study gives reassurance to the centres who have heavy workload that rescheduling oocyte
insemination or injection will not make significant difference in fertilization or utilization rates. A
small difference in ICSI cycles below 36 hours is not clinically relevant.

22. 21
Ref: Gilman A, et al. O-106 The role of intracytoplasmic sperm injection (ICSI) for non-male factor infertility in women aged 40 and over.
Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31
Supp.1, 2016.
ICSI: For Non-Male Factor Infertility in
Women 40 years and above
STUDY DETAILS
ICSI is being increasingly being used for patients without male factor, many a times without
evidence-supported indications
 Design: Retrospective Cohort Study
 Population: women, aged 40–43 years, who underwent IVF for non-male factor infertility,
at least 1 year of primary or secondary infertility
 Semen analysis (minimum requirements): 1.5 ml, 15 million sperm/ml, 39 million total
sperm, progressive motility 32%, total motility 40% and morphology 4%.
 Study Group: 229 women - conventional IVF, 491 women - ICSI
 Objective: To assess ICSI impact to improve pregnancy and live birth rates compared to
conventional IVF in women aged 40 and over
RESULTS
 Similar characteristics in two groups of maternal age (p = 0.736), paternal age (p = 0.159),
total number of oocytes collected (p = 0.120), BMI (p = 0.207), FSH dose (p = 0.119),
protocol type (p = 0.188) and number of smokers (p = 0.232).
Characteristics ICSI Group Conventional IVF Group P value
Number of MII oocytes collected 5.1 ± 3.82 6.1 ± 4.55 0.002
Day of transfer 3.3 ± 1.2 3.5 ± 1.2 0.003
Previous IVF attempts 1.1 ± 1.0 0.65 ± 0.9 0.001
Rates of IVF Failure 3% 4% 0.570
Pregnancy Rates 24.6% 29.7% 0.449
Live Birth Rates 10.2% 11.9% 0.345
 IVF had more blastocyst formation than ICSI (p=0.008)
 In Poor Ovarian Reserve (Defined by below parameters)
o Total FSH dose ≥3,000 IU (n=506): No diff in clinical preganncy rates (p=0.78)
or Live birth rate (p=0.58) in two groups
o ≤3 MII oocytes retrieved (n=99): No diff in clinical preganncy rates (p=0.45) or
Live birth rate (p=0.80)
 “CLINICAL PEARL”
ICSI does not improve pregnancy outcomes or fertilization rates in women aged 40–43 with normal
semen parameters. Conventional IVF is of benefit as it improves blastocyst formation rate.

23. 22
Ref: Hatoum I, et al. O-114 How to limit the risk of early pregnancy loss in frozen embryo transfer protocols? Abstracts of the 32nd
Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human Reproduction vol.31 Supp.1, 2016.
Early Pregnancy Loss in Frozen Embryo Transers:
How should we limit it?
STUDY DETAILS
 Design: Retrospective, Comparative study
 Population: FET cycles performed during a period of 3.5 years, embryos were derived from IVF
or ICSI procedures
 N= 1,926 cycles
 Study Group: Substituted cycles Vs stimulated cycle
o Substituted cycles: Estrogen 4–6 mg/d orally or vaginally f/b vaginal progesterone (P)
400–600 mg/d before embryo transfer to 12th
week if pregnancy occurred
o Stimulated cycle: FSH from day 4, followed 2 days after ovulation triggering by a
measure of progesteronemia
 Miscarriage: Loss of pregnancy before 14 weeks once clinical pregnancy confirmed
 Biochemical Pregnancy: beta-HCG < 100
 Early pregnancy loss (EPL): biochemical pregnancies (preclinical losses) and miscarriages.
 Objective: To assess outcomes of ART in terms of clinical pregnancy and early pregnancy loss
RESULTS
“CLINICAL PEARL”
Stimulated cycles can result physiological hormonal support via formation of corpus luteum which
results in increased live births and lower early pregnancy loss in frozen embryo transfer. RCT is
required to confirm these findings.
Early Pregnancy Loss
34.20
%
59.90
%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
Stimulated
Cycles
Substituted
Cycles
2 TIMES
INCREASED RISK
of Miscarriage with
SUBSTITUTED CYCLES
Independent of -
Age, BMI, infertilty
duration and number
of embryos
transeferred
Live Birth Rate
59.70
%
29.10
%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
Stimulated
Cycles
Substituted
Cycles

24. 23
Ref: Iliodromiti S, et al. O-125 Age at menarche, age at menopause, reproductive lifespan and risk of cardiovascular disease (CVD): a
cohort study of 256,284 women. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016.
Human Reproduction vol.31 Supp.1, 2016.
Age at Menarche and Menopause and Reproductive Lifespan:
Risk of Cardiovascular Disease
STUDY DETAILS
Longer reproductive span has lower incidence of CVD events (both fatal and non-fatal)
 Design: Randomized study
 Population: The UK Biobank, participants aged 40–70 years, White European women
 N=2,56,284
 Follow Up: 5.07 years (Interquartile range: 4.38, 5.74)
 Analysis was restricted to those without CVD and diabetes at baseline and with complete data on
exposures, outcomes and covariables.
 Objective: To assess association of early or late menarche, early menopause and reproductive age
duration with CVD risk
RESULTS
 127,949 had natural menopause / 8,686 and 8,768 diagnosed with CVD and diabetes respectively.
 1,252,915 person-years of follow up
 627 CVD events including CVD Deaths
 Reference:
o Age at Menarche: 13 years
o Age at Menopause 50-51 years
o Average duration of reproductive age: 36.7 ± 5.4 years
Parameter Adjusted Hazrad Ratio – CVD risk
Early menarche (<11 years) 1.14 (0.78, 1.66)
Late menarche (>15 years) 1.31 (0.93, 1.84)
Early Menopause (<40 years) 1.74 (1.00, 3.06)
Per 1 year long reproductive period 0.98 (0.96, 0.99)
Limitations: Age at menarche and menopause are self recorded. Nearly 50% of women had continuing
menstruation at baseline. The followp period was short.
“CLINICAL PEARL”
Longer reproductive lifespan is associated with lower risk of CVD events in middle-aged (white)
women experiencing natural menopause.

25. 24
Ref: Veleva Z, et al. O-281 Estimation of ovarian response with changing gonadotropin doses: a study of 14,805 women with repeated
stimulation cycles. Abstracts of the 32nd Annual Meeting of ESHRE, Helsinki, Finland, 3 July – 6 July, 2016. Human
Reproduction vol.31 Supp.1, 2016.
Ovarian Response with Varying Gonadotropin Doses:
Study in repeated stimulation cycles
STUDY DETAILS
 Design: Retrospective Cohort Study
 Population: Ovarian stimulation cycles for non-donor IVF/ICSI; first and second cycles of
women treated twice with the same protocol
 Databases: the US National Assisted Reproductive Technology Surveillance System, n =
26,996) and Finland (LUMI database, n = 2,614)
 N=31,096 from 39 RCTs (11 canagliflozin, 15 dapagliflozin, and 13 empagliflozin)
 Protocols: long gonadotropin-releasing hormone (GnRH) agonist (n=9175) or GnRH-
antagonist (n=5630) protocol
o Change in total gonadotropin dose in the second cycle between 4,000 and 5,000 IU
and with ≥4 oocytes retrieved in both cycles
 Outcomes: To assess changes in ovarian reposnse in repeated stimulation cycles
RESULTS
 Results were stratified by number of oocytes retrieved in the first cycle (4–10 vs. ≥11 oocytes).
 Total gonadotropin dose per oocyte: Non-linear increase with higher stimulation dose
 Dose/oocyte: inversely related to the number of oocytes retrieved
 With Long Stimulation Protocol
o Significant increase in mean stimulation dose
 [2,399.6 ± 1,995.5 to 2,606.8 ± 1,254.3 IU (P < 0.0001)]
o Significant increase in number of oocytes retrieved
 [14.4 ± 6.8 to 14.8 ± 6.9 (P = 0.02)]
o Significant increase in dose/oocyte
 [212.7 ± 180.9 to 230.9 ± 196.1 IU (P < 0.0001)]
 SIMILAR RESULTS WITH ANTAGONIST PROTOCOL
 Stratification by number of oocyte retrieved
 4–10 oocytes retrieved
o Increase of dose up to 530 (antagonist) and 600 IU (long protocol): Improved ovarian
response (lower dose/oocyte)
o Further increase of stimulation dose, response gradually worsened
 ≥11 oocytes retrieved
o Any increase in dose was associated with poorer ovarian response (higher dose/oocyte)
“CLINICAL PEARL”
Tailoring of ovarian stimulation can be done based on first cycle with unsuccessful treatment. It
may help to estimate maximal gonadotropin doses.

26. 25